This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hutchinson-Guilford progeria is caused by a mutant form of lamin A that contains an internal deletion in its C-terminal region. This prevents the proteolytic removal of the farnesylated C-terminus of lamin A that normally takes place, and leads to a toxic gain of function. To understand the molecular basis of this disease, we are carrying out proteomic analysis of nuclear envelopes isolated from the livers of mice with mutations that prevent normal removal of the lamin A farnesylated C-terminus.